Dose measurement is an important component of any medicine therapy, and especially important for an insulin therapy regimen for diabetics. To properly manage their self-therapy and communicate their conformance to a prescribed regimen, diabetics are typically required to manually record insulin injections into a logbook. Recently, a few injection pens and pen attachments have been developed for the purpose of measuring and automatically data logging the dose delivered, e.g. motorized injection pens and attachments that approximate the position of a plunger within an insulin reservoir to determine how much insulin has been delivered. However, none of the current solutions are adequate. Manual recording of insulin doses is inherently inaccurate due to human errors and omissions, and measurement of a plunger, while an improvement over manual recording, is still not accurate enough for individual doses and does not record the time that doses are delivered.
Thermal time of flight (TTOF) sensors are used to detect the time of flight of a heat pulse induced into moving fluid as it travels through a channel of known cross-section over a known distance in order to measure volumetric flow of the fluid. However, existing TTOF sensors are typically used in steady state flow scenarios, and have not to date been required to measure rapid and large changes in flow rate, as is expected in an insulin injection from an insulin pen, or the like.
There are three operating modes for a thermal flow sensor: anemometric, calorimetric and thermal time of flight (TTOF). The simplest type of thermal flow sensor is the so-called hot wire anemometer. L. V. King conducted the first systematic investigation of the hot wire anemometer in 1914, which yielded King's Law, describing the heat transfer from a cylinder of infinite length. The hot wire anemometer is simply a platinum wire inserted into a fluid flow using either a constant current or constant temperature mode of operation. Commercial thermal dispersion mass flow meters, based on constant temperature hot wire anemometry, emerged by the 1960s for industrial mass flow measurement of gases in pipes and ducts. Also in the 1960s, the capillary mass flow meter (as part of a mass flow controller) emerged to provide mass flow control at relatively low flow rates for gases in the semiconductor industry. This device uses a capillary sensor tube and a bypass, operating in calorimetric mode, by placing two platinum RTD (resistance temperature detector) windings around the capillary, which each serve as both sensor and heater. Calorimetric flow sensing has a linear relationship between the voltage output and the flow rate, but only at low flow velocities, which is the reason for the bypass configuration of the capillary based mass flow controllers. All three thermal flow sensing modes can also be applied in a MEMS-based fluid flow sensor where microfabrication is used to miniaturize and potentially mass-produce the sensor at low cost. In exemplary embodiments of the invention described herein, thin film structures serve as the heating elements and sensors. MEMS sensors also enable significant reduction of required power input. Anemometric flow sensors do not exhibit good accuracy at lower flow rates, so it is not a preferred mode for MEMS based sensors. The first MEMS thermal flow sensors (anemometric) emerged in the mid-1970s and by the 1980s it had become an active area of academic research with the first commercial thermal (calorimetric mode) MEMS airflow sensors appearing toward the end of the 1980s. MEMS flow sensors are also being adopted for mass flow controllers in place of the conventional capillary tube configuration. The design of a calorimetric MEMS sensor chip is usually a symmetrical layout on a substrate with an upstream and downstream sensor element on either side of a heating element with separation ranging from the 10s to 100s of microns. The same layout can also be used for a TTOF sensor, although utilizing the upstream sensor is not necessary unless the flow is bi-directional. Commercial MEMS thermal flow sensors are generally calorimetric, so in order to measure higher flow rates they have to be configured to operate with a bypass or increase the internal flow tube's diameter to reduce the flow velocity. The latter negatively impacts the accuracy and effective response time of the sensor. Calorimetric MEMS sensors work well for relatively low, steady-state flow conditions, such as infusion for liquid flow sensing, but do not have the accuracy, sensitivity, dynamic range, and response time necessary to accurately measure the volume of highly transient flow conditions of insulin injections. Conventional calorimetric (and TTOF) MEMS sensors that utilize a membrane as substrate cannot withstand the elevated pressure of insulin injections. TTOF sensing directly measures the velocity of the streaming fluid and therefore the volume of fluid rather than the mass flow of calorimetric (and anemometric) sensing. Microfabrication enables a TTOF sensor to attain greater accuracy because it enables submicron precision of the separation between the heating and sensing elements. Volumetric measuring is advantageous for some applications, inasmuch it is not necessary to calibrate the sensor for a specific fluid. TTOF sensing can also accurately measure flow at the much higher transient velocities of insulin injections, unlike calorimetric sensing. However, TTOF sensing is susceptible to error at very low flow rates due to thermal diffusivity in the fluid and detects a lot of noise at zero flow. Therefore, conventional TTOF sensing is not useful for detecting the onset of flow, which is very important for flow sensing over the relatively short duration of an insulin injection. Therefore, an ideal thermal flow sensor for insulin injection is a MEMS based device that is designed to operate in calorimetric mode at the onset of flow and then instantly switching to TTOF mode at a pre-selected flow rate. This type of sensor can be described as a hybrid TTOF sensor. Exemplary embodiments of the present invention, as will be described in further detail below, are designed to leverage the advantages of MEMS fabrication technology and hybrid TTOF mode operation; this results in a custom liquid volume sensor that meets the unique requirements for flow sensing during insulin injections.
Existing TTOF sensors are inadequate for sensing delivered doses of insulin injections because they lack the ability to measure the full range of flow rates typical of insulin injection, to respond instantaneously at the onset of a dosing event, and the ability to measure highly variable flow rates. In addition, conventional TTOF sensors are unable to handle the pressures associated with fluid injection devices such as syringes and pen needles.
Accordingly, there is a need for a flow sensor with a rapid sensor response time, in order to detect the transition from a zero flow state to a minimally detectable velocity. Further, there is a need for flow sensor that performs accurately from near zero flow condition and throughout the full range of flow velocities to be expected during an injection, since the velocity of fluid flow during an injection is transient during the majority of the injection cycle. There is also a need for a TTOF sensor that does not impart too much heat to the flowing insulin, since excess heat can denature or otherwise detrimentally affect the medicinal effect of the insulin. Throughout this specification, reference is made to insulin flow. However, it should be appreciated by those of ordinary skill in the art that embodiments of the invention described herein could be utilized with many medications or other fluids, and insulin should be understood to be exemplary.